1LKL

HUMAN P56-LCK TYROSINE KINASE SH2 DOMAIN IN COMPLEX WITH THE PHOSPHOTYROSYL PEPTIDE AC-PTYR-GLU-GLU-GLY (PYEEG PEPTIDE)

1LKL の概要

• エントリーDOI: 10.2210/pdb1lkl/pdb
• 分子名称: HUMAN P56 TYROSINE KINASE, PHOSPHOTYROSYL PEPTIDE AC-PTYR-GLU-GLU-GLY (3 entities in total)
• 機能のキーワード: complex (tyrosine kinase-peptide), complex (tyrosine kinase-peptide) complex, complex (tyrosine kinase/peptide)
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P06239
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 12474.70

構造登録者

Tong, L. (登録日: 1995-11-10, 公開日: 1996-03-08, 最終更新日: 2024-11-06)

主引用文献

Tong, L.,Warren, T.C.,King, J.,Betageri, R.,Rose, J.,Jakes, S.
Crystal structures of the human p56lck SH2 domain in complex with two short phosphotyrosyl peptides at 1.0 A and 1.8 A resolution.
J.Mol.Biol., 256:601-610, 1996

PubMed Abstract: src homology 2 (SH2) domains are modules of about 100 amino acid residues and bind to phosphotyrosine-containing motifs in a sequence-specific manner. They play important roles in intracellular signal transduction and represent potential targets for pharmacological intervention. The protein tyrosine kinase p56lck is a member of the src family and is involved in T-cell activation. The crystal structure of its SH2 domain with an 11-residue peptide showed that the phosphotyrosine and the Ile residue at the pY + 3 position are recognized by the SH2 domain. We present here the crystal structure of the SH2 domain of human p56lck in complex with the short phosphotyrosyl peptide Ac-pTyr-Glu-Glu-Ile (pYEEI peptide) at 1.0 A resolution. The structural analysis at atomic resolution reveals that residue Arg134 (alphaA2), which interacts with the phosphotyrosine side-chain, is present in two conformations in the complex. The structure at 1.8 A resolution of the complex with the phosphotyrosyl peptide Ac-pTyr-Glu-Glu-Gly (pYEEG peptide), which is 11 fold less potent, shows another binding mode for the pY + 3 residue as well as rearrangements of the side-chain of Arg196 (EF3) and one of the water molecules at the base of the pY + 3 pocket. The structure of the complex with the short pYEEI peptide at atomic resolution represents a good starting point for the design and optimization of new inhibitors. Comparative structural analysis of many different inhibitor complexes will be an important component of this drug discovery process.

PubMed: 8604142
DOI: 10.1006/jmbi.1996.0112

実験手法

X-RAY DIFFRACTION (1.8 Å)